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Title: Understanding erythrocytes
Description: A detailed set of notes of erythrocytes, covering their function, formation, interactions, mechanism of action, structure and more! These notes are aimed at undergraduate university students.
Description: A detailed set of notes of erythrocytes, covering their function, formation, interactions, mechanism of action, structure and more! These notes are aimed at undergraduate university students.
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8/3/19
Blood Science
Erythrocytes
Function of erythrocytes
•
Highly specialised
...
To
do this efficiently, they have certain properties:
1
...
Within the lipid bilayer there are
very few proteins embedded so it is easier for gases to move in and out
...
Haemoglobin to binds oxygen
...
3
...
The indent makes them easily
bendable without breaking
...
Absence of organelles to make room for more haemoglobin
...
Erythropoiesis
•
•
•
•
•
Formation of erythrocytes
Most common cell type in adult blood
...
7 × 106 to 6
...
2 × 106 to 5
...
4 × 106 new erythrocytes must be produced each
second
...
The rate of erythropoiesis can increase significantly from this baseline level in response to
hypoxic stress, when there is an inadequate oxygen supply due to insufficient numbers of
functional erythrocytes
...
Within the kidney, there are cells that monitor the amount of oxygen in the blood
...
It enters the blood, travels to the bone marrow and the bone marrow will accelerate the
rate of production of erythrocytes
...
Early release of Reticulocytes
• The penultimate stage of erythrocyte development is the production of reticulocytes
...
These circulating
reticulocytes eventually develop into mature erythrocytes
...
Inhibition of Apoptosis
• The body stores a significant amount of erythrocyte progenitors (CFU-E cells) in case a
higher demand is suddenly needed
...
• Epo inhibits CFU-E apoptosis to allow these cells to mature into erythrocytes
...
3
...
• Epo can accelerate these processes
...
g
...
This lessens the time it takes erythrocytes to be produced
...
It was realised that
testosterone was involved in increasing erythropoiesis levels
...
Hepcidin suppresses iron release into the circulation
...
Thus, more red blood cells will be produced
...
STAGE 2: From BFU-E cells to Colony-Forming Unit-Erythroid cell (CFU-E)
•
•
They divide and further differentiate through the mature BFU-E stage into colony-forming
unit–erythroids (CFU-E)
...
STAGE 3: From CFU-E cells to Proerythroblasts (Pronormoblast)
•
Very responsive to Epo and this stimulates the cells to rapidly proliferate and differentiate
into proerythroblasts
STAGE 4: From Proerythroblasts to Erythroblasts (Normoblast)
•
•
Iron dependency is high at this stage because it is when the most haemoglobin is produced
...
STAGE 5: From Erythroblasts to Reticulocytes
•
•
•
•
•
Erythroblasts are the last precursor cells that contain a nucleus
...
The ribosomes are subsequently destroyed
...
Stimulation by Epo results in the early release of reticulocytes into the circulation which
leads to an increase in erythrocyte number
...
Reticulocytes don’t yet have a biconcave shape
...
The reticulocytes spend several days in the spleen where macrophages perform the final
acts in erythrocyte maturation
...
Erythrocytes do not contain any organelles, no mitochondria yet they survive 120 days
...
Without mitochondria the
erythrocytes are unable to aerobically respire
...
That is enough to drive the cellular
processes
...
Colour change
2
...
Diameter of nucleus decreases then
disappears
4
...
Reduction of DNA and RN synthesis
6
...
Haemoglobin is a highly adapted protein complex for oxygen transport to tissues
...
(When the
haemoglobin reaches tissues high in CO2, the acidity increases and this makes the O2 come
off the haemoglobin and move to the tissues)
...
There are about 600 million molecules of
Hb in each mature erythrocyte
...
So, in the
presence of carbon dioxide, the hydrogen ions displace oxygen so it can diffuse out towards
the tissue
...
Iron is extracted from the diet through digestion and absorption
...
Danger of iron
•
•
•
•
Iron is physiologically essential but biochemically destructive
...
Thus, free iron can cause oxidative stress
...
g
...
Therefore, the body has developed safe mechanisms to sequester and store iron safely
...
When iron is consumed, it is in the ferric form, which is insoluble
...
Duodenal cytochrome B converts Fe 3+to Fe 2+/
...
Once inside the cell it binds to ferratin which stops it escaping
...
8/3/19
Blood Science
•
•
Hepcidin and ferroportin work together
...
Instead, the iron gets bounds to transferrin which transports it to where it is needed
...
Ferratin
• Iron complex needed to store iron in cells and remove its reactivity
...
It is a good
indicator of iron stores as a diagnostic tool
...
Transferrin
• Complexes with iron in the bloodstream, transporting it to where it needs to go
• It binds to iron when it is in the Fe 3+ state
...
• Once it has been transferred to the right place, the whole molecule is internalised into the
cell using transferrin receptors
...
• Transferrin bound to iron is called halo transferrin
...
Hepcidin
•
•
•
•
Produced in the liver and needed to regulate iron levels in bloodstream
It regulates it by binding to the iron export channel ferroportin and underregulates it by
destroying it
...
Ferroportin is also found on macrophages, which is also regulated by hepcidin
...
Ferroportin
•
The only transporter that transports iron from cell to bloodstream
...
pH is used to dissociate the iron from the transferrin by pumping protons
...
8/3/19
Blood Science
Deformability of erythrocytes
•
•
Can easily bend and flex without compromising on carrying ability
This allows erythrocytes to squeeze through very small capillaries whose width is much
smaller than the diameter of the erythrocytes
...
This allows gas exchange to be very efficient because the
erythrocyte must be touching the blood vessel to exchange gases
...
Spectrin
2
...
Ankyrin
4
...
1
The lack of organelles also allows deformability
The biconcave shape means they can easily bend due to lack of resistance
The more haemoglobin there is in a cell, the more viscous it becomes
...
The normal Mean Concentration of
Haemoglobin per Cell (MCHC) must between 32 – 36%
...
Inside the spleen, macrophages detect whether the red blood cell is suitably deformable
...
Apoptosis
•
•
•
Over the 120 days, the metabolites and proteins required have all been used up
...
During apoptosis, phospholipids flip over: those exposed to the outside of the cell are
exposed to the inside and vice versa
...
8/3/19
Blood Science
•
•
•
•
The accumulation of oxidative damage means we can no longer neutralise free radicals using
enzyme-based antioxidants e
...
- Non-enzymatic low molecular weight antioxidants like glutathione and ascorbic acid and
- Enzymatic antioxidants including superoxide dismutase, catalase, glutathione peroxidase
Over time, the anti-oxidant resources diminish and the rate of damage due to oxidative
stress increases and this results in biochemical, physical, and structural damage
...
This increase in oxidative stress increases lipid peroxidation, damaging the cell membrane
and reducing the cells deformability
Title: Understanding erythrocytes
Description: A detailed set of notes of erythrocytes, covering their function, formation, interactions, mechanism of action, structure and more! These notes are aimed at undergraduate university students.
Description: A detailed set of notes of erythrocytes, covering their function, formation, interactions, mechanism of action, structure and more! These notes are aimed at undergraduate university students.